The hair follicle, for all its highly complex morphogenesis and life-long cycling, generates individual fibers that can (given the right conditions) persist long after the death of their host, about whom they can continue to tell tales. Much of this robustness is embodied by the unique physicochemical structure of the hair shaft which limits any significant post-biogenic change. This chapter outlines the value of hair to both archaeological and forensic investigation, specifically highlighting the significance of the incremental rate of hair growth. This property enables retrieval of detailed time-resolved information for changes in diet and physiological change, toxicology, exposure to pollutants, and use of controlled substances, in addition to individualisation using DNA.

Erythema occurs in human skin following excessive exposure to ultraviolet radiation (UVR), and this is in part mediated by the vasodilator prostaglandin E2 (PGE2). While keratinocytes are a major source of this pro-inflammatory eicosanoid, epidermal melanocytes (EM) also express some of the cellular machinery required for PGE2 production. The primary aim of this study is to determine whether EM can produce PGE2 and so potentially also contribute to UVR-induced skin inflammation. Furthermore, we investigate the likely pathway by which this PGE2 production is achieved and investigate whether PGE2 production by EM is correlated with melanogenic capacity. Primary cultures of EM were established from nine normal healthy individuals with skin phototype-1 (n=4) and 4 (n=5), and PGE2 production and melanogenic status were assessed. EM produced PGE2 under baseline conditions and this was increased further upon stimulation with arachidonic acid. Moreover, EM expressed cytoplasmic phospholipase A2, cyclooxygenase-1 and cytoplasmic prostaglandin E synthase. However, no EM culture expressed cyclooxygenase-2 under baseline conditions or following arachidonic acid, UVB- or H2O2 treatments. PGE2 production in response to UVB was highly variable in EM cultures derived from different donors but when pooled for skin phototype exhibited a positive correlation only with SPT-1 derived EM. Interestingly, PGE2 production by EM in response to UVB showed no correlation with baseline levels of melanin, tyrosinase expression/activity or tyrosinase-related protein-1 expression. However, there was an apparent negative correlation with baseline expression of dopachrome tautomerase (DCT), a melanogenic enzyme with reported anti-oxidant potential. These findings suggest that EM have the potential to contribute to UVR-induced erythema via PGE2 production, but that this response may be more related to oxidative stress than to their melanogenesis status.

Surfactants are commonly used as cleansing agents and yet there are concerns they may also have a role in skin irritation. Presently, the lack of suitable methods for quantitative and qualitative analysis of surfactant deposition on skin has hindered the in-depth investigation of such effects. Here, we report the application of reverse phase liquid chromatography electrospray ionisation mass spectrometry (LC/ESI-MS/MS) assays for two surfactants commonly used in consumer products, namely sodium lauryl ether sulphate (SLES) and laurylamidopropyl betaine (LAPB), to a baseline study aiming to assess deposition levels on human skin. The linearity of the assays was established at 3-20 ng, with coefficient of variation below 5%. Detection limits were 100 pg for LAPB and 1 ng for SLES; quantitation limits were 500 pg for LAPB and 2.5 ng for SLES. The baseline study was conducted using a panel of 40 healthy volunteers. Skin extract samples were taken in triplicate from forearms, using ethanol. SLES was detected on most volunteers, with 75% of them having SLES deposits in the range of 100-600 ng/cm2. LAPB was detected on the skin of all volunteers with 85% of them having deposit levels within the concentration range of 1-100 ng/cm2. These results demonstrate the extent to which commonly used surfactants remain on the skin during the day. The analytical methods reported here can be applied to the investigation of surfactants in relation to general skin condition and the development and optimisation of new consumer wash products.

Prostanoids modulate the activity of human pregnant myometrium and their functional role can be appreciated through characterisation of prostanoid receptors and tissue concentration of prostanoids. We have applied a lipidomic approach to elucidate the profile of prostanoids in human non-labouring and labouring myometrium. We have identified a total of nineteen prostanoids including prostacyclin, thromboxanes, prostaglandins and dihydro-prostaglandins. Prostacyclin was the predominant prostanoid in both non-labouring and labouring myometria, with PGD2 and PGF2¿ being the second most abundant. Although the total amount of prostanoids was increased in the labouring tissue, PGE2 and 13,14-dihydro-15-keto-PGE2 were the only prostanoids to increase significantly at early and late labour (p¿0.001). Our data suggest that PGF2¿ plays an important role in parturition, whilst the increase in PGE2 could occur to facilitate cervical dilation and relaxation of the lower myometrium during labour. Although the elevation in TXA2 was less marked than expected, in terms of translation to function even a relatively small increase in the level of this potent spasmogen may have significant effects.

This study shows that prostaglandins in human FM55 melanoma cells and epidermal melanocytes are produced by COX-1. Prostaglandin production in FM55 melanoma cells was unrelated to that of melanin suggesting that the two processes can occur independently. ¿-Melanocyte stimulating hormone (¿-MSH), which had no effect on melanin production in FM55 cells, stimulated PGD2 production in these cells without affecting PGE2. While cAMP pathways may be involved in regulating PGD2 production, our results suggest that ¿-MSH acts independently of cAMP, possibly by regulating the activity of lipocalin-type PGD synthase. This ¿-MSH-mediated effect may be associated with its role as an immune modulator.

Chronic wounds often result from prolonged inflammation involving excessive polymorphonuclear leukocyte activity. Studies show that the omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids found in fish oils generate bioactive lipid mediators that reduce inflammation and polymorphonuclear leukocyte recruitment in numerous inflammatory disease models. The purpose of this study was to test the hypotheses that boosting plasma levels of eicosapentaenoic and docosahexaenoic acids with oral supplementation would alter lipid mediator levels in acute wound microenvironments and reduce polymorphonuclear leukocyte levels. Eighteen individuals were randomized to 28 days of either eicosapentaenoic + docosahexaenoic acid supplementation (Active Group) or placebo. After 28 days the Active Group had significantly higher plasma levels of eicosapentaenoic (p<0.001) and docosahexaenoic acid (p<0.001) than the Placebo Group and significantly lower wound fluid levels of two 15-lipoxygenase products of omega-6 polyunsaturated fatty acids, [9- hydroxyoctadecadienoic (HODE) acid (p = 0.033) and15-hydroxyeicosatrienoic acid (HETrE)
(p = 0.006)], at 24 hours post wounding. The Active Group also had lower mean levels of myeloperoxidase, a leukocyte marker, at 12 hours and significantly more re-epithelialization on Day 5 post wounding. We suggest that lipid mediator profiles can be manipulated by altering polyunsaturated fatty acid intake to create a wound microenvironment more conducive to healing.

The word ¿gerontology¿ is familiar to most of us as a term that captures the study of the social, psychological, and biological aspects of aging. However, its derivative ¿gerontobiology¿ as applied to the hair follicle is more concerned with the latter aspect ¿ the biology of aging in the hair follicle mini-organ. As with any complex multicellular tissue system, the hair follicle is prone to broadly similar underlying processes that determine the functional longevity of organs and tissues. No matter how complex the tissue system is, it will contain cells that eventually lose functionality, reproductive potential and will ultimately die. The hair follicle is somewhat unusual among mammalian tissues in that it is a veritable histologic mélange of multiple cell types (e.g., epithelial, mesenchymal and neuro-ectodermal) that function contemporaneously in all stages of their life histories e.g., stem cells, transit-amplifying cells, and terminally differentiating cells. Some of these interactive cell systems appear to be nonessential for overall hair follicle survival (e.g., melanocytes). However, strikingly graying hair follicles may grow even more vigorously than their pigmented predecessors. Moreover, the hair follicle is unique in the adult mammal in that it follows a tightly regulated script of multiple lifelong cycles of cellular birth, proliferation, differentiation, and death. Powerful evolutionary selection ensures that the hair follicle is, in the main, hardwired against significant aging-related loss of function, even after 12 or more decades of life ¿ although some would argue with this view, if only on purely cosmetic grounds. Processes underlying aging in general, e.g., oxidative damage, telomere shortening, age-relating deficiencies related to nuclear/mitochondrial DNA damage and repair as well as age-related reductions in the cells¿ energy supply, will all impact on whether some follicular cell subpopulations will enter cellular senescence. This chapter will focus on how gerontobiology of the hair follicle may impact on certain aspects of hair fiber phenotype.

There is growing interest in the use of mesenchymal stem cells (MSC) for immune therapy. Clinical trials that use MSC for treatment of therapy resistant graft versus host disease, Crohn's disease and organ transplantation have initiated. Nevertheless, the immunomodulatory effects of MSC are only partly understood. Clinical trials that are supported by basic research will lead to better understanding of the potential of MSC for immunomodulatory applications and to optimization of such therapies. In this manuscript we review some recent literature on the mechanisms of immunomodulation by MSC in vitro and animal models, present new data on the secretion of pro-inflammatory and anti-inflammatory cytokines, chemokines and prostaglandins by MSC under resting and inflammatory conditions and discuss the hopes and expectations of MSC-based immune therapy.

As a highly visual and social species we communicate significantly via our physical appearance. Thus, it is unsurprising that the phenotypic aspects (including color) of our skin and hair feature prominently in such communication. Perhaps, one of the more potent reminders of aging is the change in pigmentation from birth to puberty and through to young adulthood, middle age, and beyond. Indeed, the hair bulb melanocyte may be viewed as an exquisitely sensitive aging sensor. In this context, we can appreciate that the loss of pigmentation from the hair tends to be earlier and much more striking than the age-associated pigmentation changes that we see in the epidermis. This phenotypic difference between the hair follicle and the epidermis-melanocyte subpopulations is of considerable interest, not least as both subpopulations originate from the same embyrologic neural crest and that the melanoctye stem cells in the adult hair follicle can occupy vacant niches in the epidermis. A major source of the differential aging of melanocytes in the hair bulb vs. the epidermis is likely due to the former¿s stringent coupling to the hair growth cycle when compared with the latter¿s continuous and UV-sensitive melanogenesis. Also likely to be involved is the maintenance of permissive microenvironments in these different skin compartments including their differing redox environments and variable connectivity with neuroendocrine axis. Over the last few years, we and others have striven to develop advanced cell culture methodologies for isolated hair follicle melanocytes and for intact anagen hair follicle organ culture, which may provide research tools to elucidate the regulatory mechanisms of hair follicle pigmentation. Others have assessed the robustness of the hair follicle-melanocyte stem compartment with age and other functional stressors. In the long term, it may be feasible to develop strategies to modulate some of these aging-associated changes in the hair follicle that impinge particularly of the melanocyte populations.

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